NADH-ubiquinone oxidoreductase chain 4

Details

Name
NADH-ubiquinone oxidoreductase chain 4
Synonyms
  • 1.6.5.3
  • MTND4
  • NADH dehydrogenase subunit 4
  • NADH4
  • ND4
Gene Name
MT-ND4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010383|NADH-ubiquinone oxidoreductase chain 4
MLKLIVPTIMLLPLTWLSKKHMIWINTTTHSLIISIIPLLFFNQINNNLFSCSPTFSSDP
LTTPLLMLTTWLLPLTIMASQRHLSSEPLSRKKLYLSMLISLQISLIMTFTATELIMFYI
FFETTLIPTLAIITRWGNQPERLNAGTYFLFYTLVGSLPLLIALIYTHNTLGSLNILLLT
LTAQELSNSWANNLMWLAYTMAFMVKMPLYGLHLWLPKAHVEAPIAGSMVLAAVLLKLGG
YGMMRLTLILNPLTKHMAYPFLVLSLWGMIMTSSICLRQTDLKSLIAYSSISHMALVVTA
ILIQTPWSFTGAVILMIAHGLTSSLLFCLANSNYERTHSRIMILSQGLQTLLPLMAFWWL
LASLANLALPPTINLLGELSVLVTTFSWSNITLLLTGLNMLVTALYSLYMFTTTQWGSLT
HHINNMKPSFTRENTLMFMHLSPILLLSLNPDIITGFSS
Number of residues
459
Molecular Weight
51580.26
Theoretical pI
9.67
GO Classification
Functions
NADH dehydrogenase (ubiquinone) activity
Processes
aging / cellular metabolic process / cerebellum development / in utero embryonic development / mitochondrial electron transport, NADH to ubiquinone / respiratory electron transport chain / response to ethanol / response to hypoxia / response to nicotine / small molecule metabolic process
Components
integral component of membrane / mitochondrial inner membrane / mitochondrial respiratory chain complex I
General Function
Nadh dehydrogenase (ubiquinone) activity
Specific Function
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity).
Pfam Domain Function
Transmembrane Regions
22-42 60-80 102-122 145-165 196-216 224-244 257-277 284-303 308-330 351-371 391-411
Cellular Location
Mitochondrion membrane
Gene sequence
>lcl|BSEQ0010384|NADH-ubiquinone oxidoreductase chain 4 (MT-ND4)
ATGCTAAAACTAATCGTCCCAACAATTATATTACTACCACTGACATGACTTTCCAAAAAA
CACATAATTTGAATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCCTCTACTA
TTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTTTTCCTCCGACCCC
CTAACAACCCCCCTCCTAATACTAACTACCTGACTCCTACCCCTCACAATCATGGCAAGC
CAACGCCACTTATCCAGTGAACCACTATCACGAAAAAAACTCTACCTCTCTATACTAATC
TCCCTACAAATCTCCTTAATTATAACATTCACAGCCACAGAACTAATCATATTTTATATC
TTCTTCGAAACCACACTTATCCCCACCTTGGCTATCATCACCCGATGAGGCAACCAGCCA
GAACGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTCCCTTCCCCTA
CTCATCGCACTAATTTACACTCACAACACCCTAGGCTCACTAAACATTCTACTACTCACT
CTCACTGCCCAAGAACTATCAAACTCCTGAGCCAACAACTTAATATGACTAGCTTACACA
ATAGCTTTTATAGTAAAGATACCTCTTTACGGACTCCACTTATGACTCCCTAAAGCCCAT
GTCGAAGCCCCCATCGCTGGGTCAATAGTACTTGCCGCAGTACTCTTAAAACTAGGCGGC
TATGGTATAATACGCCTCACACTCATTCTCAACCCCCTGACAAAACACATAGCCTACCCC
TTCCTTGTACTATCCCTATGAGGCATAATTATAACAAGCTCCATCTGCCTACGACAAACA
GACCTAAAATCGCTCATTGCATACTCTTCAATCAGCCACATAGCCCTCGTAGTAACAGCC
ATTCTCATCCAAACCCCCTGAAGCTTCACCGGCGCAGTCATTCTCATAATCGCCCACGGG
CTTACATCCTCATTACTATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGC
ATCATAATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATAGCTTTTTGATGACTT
CTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTACTGGGAGAACTCTCT
GTGCTAGTAACCACGTTCTCCTGATCAAATATCACTCTCCTACTTACAGGACTCAACATA
CTAGTCACAGCCCTATACTCCCTCTACATATTTACCACAACACAATGGGGCTCACTCACC
CACCACATTAACAACATAAAACCCTCATTCACACGAGAAAACACCCTCATGTTCATACAC
CTATCCCCCATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTT
Chromosome Location
Not Available
Locus
-
External Identifiers
ResourceLink
UniProtKB IDP03905
UniProtKB Entry NameNU4M_HUMAN
GenBank Gene IDJ01415
GenAtlas IDMT-ND4
HGNC IDHGNC:7459
General References
  1. Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG: Sequence and organization of the human mitochondrial genome. Nature. 1981 Apr 9;290(5806):457-65. [PubMed:7219534]
  2. Lu X, Walker T, MacManus JP, Seligy VL: Differentiation of HT-29 human colonic adenocarcinoma cells correlates with increased expression of mitochondrial RNA: effects of trehalose on cell growth and maturation. Cancer Res. 1992 Jul 1;52(13):3718-25. [PubMed:1377597]
  3. Silva WA Jr, Bonatto SL, Holanda AJ, Ribeiro-Dos-Santos AK, Paixao BM, Goldman GH, Abe-Sandes K, Rodriguez-Delfin L, Barbosa M, Paco-Larson ML, Petzl-Erler ML, Valente V, Santos SE, Zago MA: Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America. Am J Hum Genet. 2002 Jul;71(1):187-92. Epub 2002 May 17. [PubMed:12022039]
  4. Moilanen JS, Finnila S, Majamaa K: Lineage-specific selection in human mtDNA: lack of polymorphisms in a segment of MTND5 gene in haplogroup J. Mol Biol Evol. 2003 Dec;20(12):2132-42. Epub 2003 Aug 29. [PubMed:12949126]
  5. Ingman M, Kaessmann H, Paabo S, Gyllensten U: Mitochondrial genome variation and the origin of modern humans. Nature. 2000 Dec 7;408(6813):708-13. [PubMed:11130070]
  6. Ingman M, Gyllensten U: Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines. Genome Res. 2003 Jul;13(7):1600-6. [PubMed:12840039]
  7. Coble MD, Just RS, O'Callaghan JE, Letmanyi IH, Peterson CT, Irwin JA, Parsons TJ: Single nucleotide polymorphisms over the entire mtDNA genome that increase the power of forensic testing in Caucasians. Int J Legal Med. 2004 Jun;118(3):137-46. Epub 2004 Feb 4. [PubMed:14760490]
  8. Brown WM, Prager EM, Wang A, Wilson AC: Mitochondrial DNA sequences of primates: tempo and mode of evolution. J Mol Evol. 1982;18(4):225-39. [PubMed:6284948]
  9. Chomyn A, Mariottini P, Cleeter MW, Ragan CI, Matsuno-Yagi A, Hatefi Y, Doolittle RF, Attardi G: Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase. Nature. 1985 Apr 18-24;314(6012):592-7. [PubMed:3921850]
  10. Murray J, Zhang B, Taylor SW, Oglesbee D, Fahy E, Marusich MF, Ghosh SS, Capaldi RA: The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. J Biol Chem. 2003 Apr 18;278(16):13619-22. Epub 2003 Feb 28. [PubMed:12611891]
  11. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  12. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712]
  13. Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, Elsas LJ 2nd, Nikoskelainen EK: Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science. 1988 Dec 9;242(4884):1427-30. [PubMed:3201231]
  14. Majander A, Huoponen K, Savontaus ML, Nikoskelainen E, Wikstrom M: Electron transfer properties of NADH:ubiquinone reductase in the ND1/3460 and the ND4/11778 mutations of the Leber hereditary optic neuroretinopathy (LHON). FEBS Lett. 1991 Nov 4;292(1-2):289-92. [PubMed:1959619]
  15. Kormann BA, Schuster H, Berninger TA, Leo-Kottler B: Detection of the G to A mitochondrial DNA mutation at position 11778 in German families with Leber's hereditary optic neuropathy. Hum Genet. 1991 Nov;88(1):98-100. [PubMed:1959931]
  16. Marzuki S, Noer AS, Lertrit P, Thyagarajan D, Kapsa R, Utthanaphol P, Byrne E: Normal variants of human mitochondrial DNA and translation products: the building of a reference data base. Hum Genet. 1991 Dec;88(2):139-45. [PubMed:1757091]
  17. Lertrit P, Noer AS, Jean-Francois MJ, Kapsa R, Dennett X, Thyagarajan D, Lethlean K, Byrne E, Marzuki S: A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I. Am J Hum Genet. 1992 Sep;51(3):457-68. [PubMed:1323207]
  18. De Vries DD, Went LN, Bruyn GW, Scholte HR, Hofstra RM, Bolhuis PA, van Oost BA: Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia. Am J Hum Genet. 1996 Apr;58(4):703-11. [PubMed:8644732]
  19. Sudoyo H, Sitepu M, Malik S, Poesponegoro HD, Marzuki S: Leber's hereditary optic neuropathy in Indonesia: two families with the mtDNA 11778G>A and 14484T>C mutations. Hum Mutat. 1998;Suppl 1:S271-4. [PubMed:9452107]
  20. Calvo SE, Tucker EJ, Compton AG, Kirby DM, Crawford G, Burtt NP, Rivas M, Guiducci C, Bruno DL, Goldberger OA, Redman MC, Wiltshire E, Wilson CJ, Altshuler D, Gabriel SB, Daly MJ, Thorburn DR, Mootha VK: High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Nat Genet. 2010 Oct;42(10):851-8. doi: 10.1038/ng.659. Epub 2010 Sep 5. [PubMed:20818383]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00157NADHapproved, nutraceuticalunknownDetails